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对曾在儿童期接受过生长激素治疗的普拉德-威利综合征青年成人进行三年生长激素治疗:对葡萄糖稳态和代谢综合征的影响。

Three years of growth hormone treatment in young adults with Prader-Willi Syndrome previously treated with growth hormone in childhood: Effects on glucose homeostasis and metabolic syndrome.

作者信息

Damen Layla, Grootjen Lionne N, Donze Stephany H, Juriaans Alicia F, de Graaff Laura C G, van der Velden Janielle A E M, Hokken-Koelega Anita C S

机构信息

Dutch Growth Research Foundation, Rotterdam, The Netherlands.

Department of Pediatrics, Subdivision of Endocrinology, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.

出版信息

Clin Endocrinol (Oxf). 2020 Oct;93(4):439-448. doi: 10.1111/cen.14274. Epub 2020 Jul 22.

Abstract

CONTEXT

Growth hormone (GH) has been approved for children with Prader-Willi syndrome (PWS) and significantly improves body composition in adults with PWS. Adults with PWS are predisposed to develop impaired glucose tolerance (IGT) and diabetes mellitus type 2 (DMT2). Continuation of GH maintains body composition, but GH is known to induce insulin resistance, which might affect glucose homeostasis. Studies on long-term effects of GH treatment in adults are very limited.

OBJECTIVE

To investigate effects of 3 years of GH treatment on glucose homeostasis and prevalence of metabolic syndrome (MS) in adults with PWS.

DESIGN

Open-label, prospective study.

PATIENTS

43 young adults with PWS.

SETTING

Dutch PWS Reference Center.

MAIN OUTCOME MEASURES

Glucose and insulin during oral glucose tolerance test.

RESULTS

Estimated mean (95% CI) fasting glucose and insulin levels remained stable during 3 years of GH treatment. Glucose being 4.6 (4.4-4.8) mmol/l at start and 4.7 (4.6-4.9) mmol/l after 3 years (P = .07); insulin being 59.5 (45.2-75.8) pmol/l and 56.7 (45.2-69.6) pmol/l resp. (P = .72). Sex, ethnicity and fat mass percentage were significantly associated with fasting glucose levels, while IGF-I or GH-dose were not. Blood pressure, lipids and prevalence of MS remained stable during 3 years of GH. IGT prevalence was variable over time, six patients had IGT at start and eleven after 3 years of GH. One patient developed DMT2. However, prevalence of IGT or DMT2 was not significantly higher after 3 years than at study start.

CONCLUSIONS

Three years of GH treatment in adults with PWS does not impair glucose homeostasis and does not lead to an increased prevalence of DMT2.

摘要

背景

生长激素(GH)已被批准用于普拉德-威利综合征(PWS)儿童,并且能显著改善PWS成人患者的身体组成。PWS成人患者易发生糖耐量受损(IGT)和2型糖尿病(DMT2)。继续使用GH可维持身体组成,但已知GH会诱导胰岛素抵抗,这可能影响葡萄糖稳态。关于GH治疗对成人长期影响的研究非常有限。

目的

研究3年GH治疗对PWS成人患者葡萄糖稳态及代谢综合征(MS)患病率的影响。

设计

开放标签的前瞻性研究。

患者

43例年轻的PWS成人患者。

地点

荷兰PWS参考中心。

主要观察指标

口服葡萄糖耐量试验期间的血糖和胰岛素水平。

结果

在3年的GH治疗期间,估计的平均(95%CI)空腹血糖和胰岛素水平保持稳定。开始时血糖为4.6(4.4 - 4.8)mmol/L,3年后为4.7(4.6 - 4.9)mmol/L(P = 0.07);胰岛素分别为59.5(45.2 - 75.8)pmol/L和56.7(45.2 - 69.6)pmol/L(P = 0.72)。性别、种族和脂肪质量百分比与空腹血糖水平显著相关,而IGF-I或GH剂量则不然。在3年的GH治疗期间,血压、血脂和MS患病率保持稳定。IGT患病率随时间变化,6例患者开始时患有IGT,3年GH治疗后有11例。1例患者发生了DMT2。然而,3年后IGT或DMT2的患病率并不比研究开始时显著更高。

结论

对PWS成人患者进行3年的GH治疗不会损害葡萄糖稳态,也不会导致DMT2患病率增加。

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